International Drug Abuse Research Society ( IDARS )

What is IDARS?
“IDARS” is an acronym for the International Drug Abuse Research Society. The purposes of IDARS are scientific, educational and charitable. The Society seeks to promote excellence in: 1) advancing the understanding of drug abuse, substance abuse, and addiction, 2) bringing together scientists of varying backgrounds and disciplines within the field of drug abuse research, 3) integrating drug abuse research directed at all levels of biological organization to improve prevention and treatment efforts, 4) promoting education in the addiction sciences, 5) informing the general public about the results and implications of current research in the addiction sciences.

Who are the members of IDARS?
Members of IDARS are research scientists and clinicians from around the world. The current president of IDARS is Dr. Michael J. Kuhar, Professor of Pharmacology, at the Yerkes National Primate Center of Emory University, in Atlanta, GA. The Executive Officer is Dr. Syed F. Ali, Head, Neurochemistry Laboratory, Division of Neurotoxicology, at the National Toxicological Research Center, Food and Drug Administration, in Jefferson, AR.

IDARS has 3 categories of membership.
Regular Members: Any credentialed research scientist or health professional working in the field of substance abuse may be considered for Regular Membership. Annual dues are $50.
Student and Post-Doctoral Fellow Members: Any post-baccalaureate student matriculated in an advanced degree program, or anyone participating in a post-doctoral training program, in a field related to drug abuse research, may be considered for this category of membership. Annual dues are $20.
Emeritus Members: Upon retirement, any member of IDARS may apply for Emeritus status. In some cases, distinguished scientists will be nominated for Emeritus membership. There are no annual dues for Emeritus members.

When does IDARS meet?
IDARS will have annual meetings, where members and non-members alike can share their most recent research data. IDARS plans to hold its first meeting in Spring 2006 in Washington, DC. This year, many members of IDARS will attend a scientific conference entitled, “Cellular and Molecular Mechanisms of Drugs of Abuse and Neurotoxicity: Cocaine, GHB and Substituted Amphetamines”, which will take place from August 16-19, in Venice, Italy. The Venice conference is an official Pre-Satellite meeting of the 20th Biennial meeting of the International Society for Neurochemistry (ISN), held jointly with the European Society for Neurochemistry (ESN).

Worldwide Stimulant Abuse – An Emerging Health Crisis
“Stimulant” drugs produce a spectrum of effects that includes increased energy, cardiovascular stimulation, heightened mood and decreased need for sleep. After high doses or long periods of use, stimulants can produce a range of medical complications including heart attacks, strokes, psychotic episodes and seizures. From a molecular perspective, most stimulants interact with monoamine transporter proteins found on nerve cells. Stimulant drugs can be divided into two classes based on their transporter-mediated mechanisms of action: monoamine transporter blockers (i.e., cocaine) and substrate-type monoamine releasers (i.e., amphetamines) [reviewed in Baumann and Rothman, 2003]. It is noteworthy that many stimulants are useful medications with long histories of safety and efficacy, whereas others are highly addictive substances associated with considerable morbidity and mortality. Illicit stimulants are some of most commonly abused drugs worldwide – during the year 2000, it is estimated that 34.3 million people used amphetamines, 14.1 million used cocaine, and 7.7 million used the amphetamine analog, 3,4,-methylenedioxymethamphetamine (MDMA) [UNODC, 2003]. Such evidence supports the emergence of stimulant abuse as global health crisis.

“Super Coke” In Colombia – It’s the Real Thing!
The abuse of cocaine continues to be a problem in the US and other nations around the world. Colombia remains the number one producer of marketable cocaine hydrochloride and provides more than 80% of global supply. Figure 1 shows the explosive growth in Colombian cocaine production in the past few years. Cocaine alkaloid is extracted from the coca plant, Erythroxylaceae coca, which is cultivated throughout the Andean region (see Figure 2). Recently, anti-drug operatives in Colombia have identified genetically-modified (GM) coca plants that produce yields of cocaine much greater than normal. The “super coke” plants grow to heights of 7-9 ft whereas typical coca plants grow to heights of 3-4 ft. Furthermore, the GM plants are resistant to herbicides and produce up to 5-times more cocaine alkaloid than normal plants. The discovery of transgenic coca plants adds a troubling new dimension to the spread of cocaine abuse.

Few treatments options are available for cocaine-dependent patients, and the development of medications to combat cocaine addiction is a major challenge for biomedical research. IDARS scientists have discovered novel approaches for treating cocaine dependence. Christian Heidbreder and colleagues at Glaxo-Smith-Kline have identified and tested the selective dopamine D3 receptor antagonist, SB277011A as a potential treatment for cocaine dependence [reviewed in Heidbreder and Hagan, 2005]. In animal models, SB277011A blocks the ability of cocaine and stress to induce reinstatement of cocaine-seeking behavior [Xi et al., 2004]. Moreover, SB277011A appears to reduce drug-seeking behavior in general, suggesting that D3 antagonists could have anti-addictive efficacy in the treatment of nicotine, opioid and stimulant dependence.

“Ya-Ba” Da-Ba Doom in Thailand
Similar to the cocaine crisis, the abuse of methamphetamine is increasing in the US and abroad. One of worst epidemics of methamphetamine abuse is occurring in Thailand, where 70% of drug addicts, or 2.5 million people, are dependent upon methamphetamine. Most users ingest a tablet formulation of methamphetamine known as “Ya-Ba”, meaning “crazy medicine”. Figure 3 depicts the typical appearance of Ya-Ba tablets. Nearly all Ya-Ba confiscated in Thailand is produced in the neighboring country of Burma, by the drug-trafficking insurgent group, the United Wa State Army (USWA). USWA and other such groups pose a significant threat to the national security of countries in South East Asia and elsewhere. It is estimated that Burmese methamphetamine production exceeds 800 million tablets per year. Figure 4 shows Thai police prepared to destroy large quantities of confiscated Ya-Ba tablets.

The long-term effects of methamphetamine abuse in humans are not well studied, but in rodents, methamphetamine causes depletions of dopamine and serotonin in the brain. Methamphetamine-induced loss of monoamines could underlie depression and suicidal ideation that often accompany drug withdrawal. Members of IDARS have shown that methamphetamine can cause neurotoxic effects. Francesco Fornai and colleagues at the University of Pisa, in Italy, demonstrated that mice treated with methamphetamine display abnormal dopamine cells in the brain [Fornai et al., 2004a]. The affected cells have intracellular inclusions which resemble those found in Parkinson’s disease and other neurodegenerative disorders. Methamphetamine produces similar inclusions in cultured PC12 cells. While the clinical relevance of these data is uncertain, they suggest that methamphetamine abuse could predispose individuals to neurodegenerative disorders [Fornai et al., 2004b].

Ecstasy in the UK and Beyond: It’s Nothing to Rave About!
The “rave” scene continues to be major source of drug abuse in the UK, throughout Europe, and in the US. In particular, the substituted amphetamine MDMA (Ecstasy, or E) is commonly abused at all night dance parties, or raves. Users often take multiple doses of MDMA at once (i.e., “stacking”) or take supplemental doses of the drug repeatedly during the party (i.e., “bumping”). Figure 5 shows some examples of MDMA tablets. US statistics show that medical complications associated with MDMA use have risen exponentially – MDMA-related emergency room visits increased from 253 in 1994 to 4026 in 2002. Young people continue to experiment with MDMA despite the risk of adverse effects including depression, cognitive disturbances and memory problems. Figure 6 depicts a popular DVD program, “Generation E”, that describes the rave culture and criticizes attempts by the US government to criminalize rave-related activities.

The long-term consequences of MDMA abuse in humans are not well understood, and there is disagreement concerning the reinforcing properties of MDMA in animals and humans. IDARS scientists are exploring the potential addictive properties of MDMA. Susan Schenk and colleagues at University of Wellington, in New Zealand, have developed a novel paradigm where rats learn to self-administer MDMA [Schenk et al., 2003]. Their work shows that MDMA is a positive reinforcer in rats, and prior experience with cocaine engenders more rapid acquisition of MDMA intake. Dopamine appears to be involved in the addictive properties of MDMA, since D1 dopamine receptor antagonists reduce self-administration of the drug [Daniela et al., 2004]. These findings may have implications for the development of treatments for MDMA addiction.

New “Legal Highs” in New Zealand
A number of non-amphetamine designer drugs have appeared on internet websites where they are marketed as “legal Ecstasy”. In particular, the substituted piperazine analogs 1-benzylpiperazine (BZP, or ‘A2’) and 1-(m-trifluoromethylphenyl)piperazine (TFMPP, or ‘Molly’) are increasingly trafficked in the US, Europe, and elsewhere. BZP produces amphetamine-like stimulant effects in humans, suggesting the potential for abuse. Figure 7 shows BZP tablets confiscated by US authorities. The US DEA has moved swiftly to place BZP in Schedule 1 of the Controlled Substances Act, making possession of this substance a criminal offense. In other places, however, BZP is legally available. A significant level of BZP abuse is occurring in New Zealand, where BZP is widely sold over the internet and at “party pill” shops. Figure 8 depicts the Rave.Net.NZ website, a popular site for sharing information about the rave scene in New Zealand.

The pharmacology of BZP, and other substituted piperazines, is not well characterized, but available data suggest that BZP has stimulant properties. Members of IDARS are examining the neurobiological effects of BZP in animal models. Michael Baumann and colleagues at the NIDA IRP have shown BZP interacts with monoamine transporters to release dopamine and serotonin from brain tissue in vitro [Baumann et al., 2005]. Microdialysis studies in rats show that BZP causes elevations in extracellular monoamines that are similar to the effects of methamphetamine. Likewise, self-administration studies in monkeys demonstrate that BZP is a powerful reinforcer with significant abuse liability [Fantegrossi et al., 2005]. The long-term effects of BZP are unexplored and warrant further investigation.

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